Year 2017 / Volume 109 / Number 1
Original
Influence of sustained viral response on the regression of fibrosis and portal hypertension in cirrhotic HCV patients treated with antiviral triple therapy

17-25

DOI: 10.17235/reed.2016.4235/2016

Ángela Puente, Joaquín Cabezas, María Jesús López Arias, José Ignacio Fortea, María Teresa Arias, Ángel Estébanez, Fernando Casafont, Emilio Fábrega, Javier Crespo,

Abstract
Background and aims: The regression of liver fibrosis and portal hypertension (PH) and their influence on the natural history of compensated hepatitis C virus (HCV)-related cirrhosis has not been studied previously. Our objective was to evaluate the influence of sustained virologic response (SVR) on the portal pressure gradient (HVPG) and non-invasive parameters of PH and prognostic factors of response. Methods: Sixteen patients with compensated HCV genotype 1-related cirrhosis with PH (HVPG > 6 mmHg) without beta-blocker therapy were considered as candidates for PEGα2a + RBV + BOC (48 weeks; lead-in and accepted stopping rules). A hemodynamic study and Fibroscan® were performed at baseline, at eight weeks and, in the case of SVR, 24 weeks after treatment. In each hemodynamic study, serum samples were analyzed for inflammatory biomarkers associated with PH. Results: In eight cases, SVR was obtained; five patients relapsed, and treatment was stopped early for non-response to lead in (one case) and a decrease of < 3 log at week 8 (two patients). Compared to baseline, there was a significant decrease in HVPG and Fibroscan® at weeks 8 and 72 (10.31 ± 4.3 vs 9.4 ± 5.04 vs 6.1 ± 3.61 mmHg, p < 0.0001 and 21.3 ± 14.5 vs 16.2 ± 9.5 vs 6.4 ± 4.5 kPa, p < 0.0001, respectively). The average HVPG decrease in SVR was 40.8 ± 17.53%, achieving an HVPG < 6 mmHg in five patients (62.5%) and a Fibroscan® < 7.1 kPa in three patients (37.5%). Conclusions: Complete hemodynamic response (HVPG < 6 mmHg) and fibrosis regression (Fibroscan® < 7.1 kPa) occur in more than half and one-third of patients achieving SVR, respectively, and must be another target in cirrhotic patients with SVR.
Share Button
New comment
Comments

04/03/2019 10:51:46
Great article . I want to get to increase my knowledge


References
1. Bacon BR, Gordon et al. Boceprevir for Previously Treated Chronic HCV Genotype 1 Infection. N Engl J Med 2011; 364:1207-1217
2. Poordad F, McCone J Jr, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011; 364:1195-206.
3. Hézode C, Fontaine H, et al; CUPIC Study Group. Effectiveness of telaprevir or boceprevir in treatment-experienced patients with HCV genotype 1 infection and cirrhosis. Gastroenterology. 2014 Jul;147(1):132-142.
4.Hézode C, Fontaine H, et al ;CUPIC Study Group. Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicenter cohort of the French Early Access Programme (ANRS CO20-CUPIC). J Hepatol. 2013 Sep; 59(3):434-41
5.Calleja JL, Pascasio JM, et al ; the Spanish Group for the Study of the Use of Direct-Acting Drugs Hepatitis C with Severe Fibrosis. Safety and efficacy of triple therapy with peginterferon, ribavirin and boceprevir within an early access programme in Spanish patients with hepatitis C genotype 1 with severe fibrosis: SVRw12 analysis. Liver Int. 2014 Aug 11.
6. Shiratori Y, Imazaki F, et al. Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med 2000;132:617-24.
7. Poynard T, McHutchison J, et al. Impact of pegylated interferon alfa 2b and ribavirin on liver fibrosis in patients with cronic hepatitis C. Gastroenterology 2002;122:1303-13.
8. Roberts S, Gordon A, et al. Effect of sustained viral response on hepatic venous pressure gradient in hepatitis C-related cirrhosis. Clin Gastroenterol Hepatol 2007;5:932–937
9. Burroughs AK, Groszmann R, et al. Assessment of therapeutic benefit of antiviral therapy in chronic hepatitis C: is hepatic venous pressure gradient a better end point? Gut 2002; 50:425–427
10. Rincon D, Ripoll C, et al. Antiviral therapy decreases hepatic venous pressure gradient in patients with chronic hepatitis C and advanced fibrosis. Am J Gastroenterol 2006; 101:2269–2274.
11. Thomopoulos KP, CLabropoulou-Karatza C, et al. And GIconomou. Non-invasive predictors of the presence of large oesophageal varices in patients with cirrhosis Dig Liver Dis. 2003 Jul;35(7):473-8.
12. Castera L, Forns x and Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography, J Hepatol 48 (2008), 835–847.
13. Robic M, Procopet B , et al .Liver stiffness accurately predicts portal hypertension related complications in patients with chronic liver disease: a prospective study. J Hepatol. 2011 Nov;55(5):1017-24
14. Talwalkar JA, Kurtz M, et al. Ultrasound-based transient elastography for the detection of hepatic fibrosis: systematic review and metaanalysis, Clin Gastroenterol Hepatol 5 (2007), 1214–1220.
15. Friedrich-Rust M, Ong MF, et al., Performance of transient elastography for the staging of liver fibrosis: a meta-analysis, Gastroenterology 134 (2008), 960–974.
16. Castera L, Foucher J, et al., Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations, Hepatology 51 (2010), 828–835.
17. Vizzutti F, Arena U, et al., Liver stiffness measurement predicts severe portal hypertension in patients with HCV-related cirrhosis, Hepatology 45 (2007), 1290–1297.
18. Berzigotti A, Seijo S, et al. Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis. Gastroenterology 2013;144:102-111.
19. Colecchia A ,Montrone L, et al. Measurement of spleen stiffness to evaluate portal hypertension and the presence of esophageal varices in patients with HCV-related cirrhosis.Gastroenterology. 2012 Sep;143(3):646-54
20. Augustin S, Millán L, González A, Martell M. Detection of early portal hypertension with routine data and liver stiffness in patients with asymptomatic liver disease: a prospective study. J Hepatol. 2014 Mar;60(3):561-9.
21. G. Sebastiani, D. Tempesta, et al , Prediction of oesophageal varices in hepatic cirrosis by simple serum non-invasive markers: Results of a multicenter, large-scale study, J Hepatol 53 (2010), 630–638.
22. M. Kondo, S.J. Miszputen, et al. The predictive value of serum laminin for the risk of variceal bleeding related to portal pressure levels, Hepatogastroenterology 42 (1995), 542–545.
23. J. Kropf, A.M. Gressner and W. Tittor, Logistic-regression model for assessing portal hypertension by measuring hyaluronic acid (hyaluronan) and laminin in serum, Clin Chem 37 (1991), 30–35.
24. Buck M, Garcia-Tsao G, et al .Novel inflammatory biomarkers of portal pressure in compensated cirrhosis patients.Hepatology. 2014 Mar;59(3):1052-9.
25. Reiberger T, Rutter K,et al. Portal pressure predicts outcome and safety of antiviral therapy in cirrhotic patients with hepatitis C virus infection. Clin Gastroenterol Hepatol. 2011 Jul;9(7):602-8
26. García-Tsao G, Rodiguez-Perez F, BleiaT, et al. Treatment with interferon reduces portal pressure in patients with chronic hepatitis C. A randomized placebo trial. Gastroenterology 1996;10:A1193.
27. Van der Meer AJ, Veldt BJ, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012 Dec 26;308(24):2584-93
28. Aleman S, Rahbin N, et al. A risk for hepatocellular carcinoma persists long-term after sustained virologic response in patients with hepatitis C-associated liver cirrhosis. Clin Infect Dis. 2013 Jul;57(2):230-6
29. Mallet V,Gilgenkrantz H, et al. The Relationship of Regression of Cirrhosis to Outcome in Chronic Hepatitis C. Ann Intern Med. 2008;149(6):399-403
30. D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006 Jan;44(1):217-31.
31.Ogawa E, Furusyo N, et al. Non-invasive fibrosis assessment predicts sustained virological response to telaprevir with pegylated interferon and ribavirin for chronic hepatitis C. Antivir Ther. 2014 Jun 18.
32. Shiratori Y, Imazeki F, et al. Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med 2000;132:517–24.
33. Ballet F, Chretien Y, Rey C, et al. Differential response of normal and cirrhotic liver to vasoactive agents. A study in the isolated perfused rat liver. J Pharmacol Exp Ther 1988;244:283–9.
34. Carluccio MA, Ancora MA, et al. Homocysteine induces VCAM-1 gene expression through NF-kappaB and NAD(P)H oxidase activation: protective role of Mediterranean diet polyphenolic antioxidants. Am J Physiol Heart Circ Physiol 2007;293:
35. Oertli B, Beck-Schimmer B, et al. Mechanisms of hyaluronan-induced up-regulation of ICAM-1 and VCAM-1 expression by murine kidney tubular epithelial cells: hyaluronan triggers cell adhesion molecule expression through a mechanism involving activation of nuclear factor-kappa B and activating protein-1. J Immunol 1998;161: 3431-3437.
36. Rutter K, Ferlitsc A, et al. Safety of triple therapy with telaprevir or boceprevir in hepatitis c patients with advanced liver disease – predictive factors for sepsis. Journal of Hepatology, Suppl 1, Apr 2013. Abs 65.
37.Albillos, A, de la Hera, A.et al. Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement. Hepatology. 2003; 37: 208–217
38.Wiest, R. and Garcia-Tsao, G. Bacterial translocation in liver cirrhosis. Hepatology. 2005; 41: 422–433
39. Tandon, P. and Garcia-Tsao, G. Bacterial infections, sepsis, and multiorgan failure in cirrhosis. Semin Liver Dis. 2008; 28: 26–42
40. Afdhal N, Everson G, et al. Effect of long term Viral suppression with Sofosvubir + Ribavirin on hepatic venous pressure gradient in HCV infected patients with cirrhosis and portal hypertension. EASL congress 2015. Abstract LP13
41. Vergiol J , Foucher J, Castera Let al Changes of non-invasive markers and FibroScan values during HCV treatment. J Viral Hepat. 2009 Feb;16(2):132-40.
Related articles

Editorial

Treatment of portal vein thrombosis in cirrhosis patients

DOI: 10.17235/reed.2023.9800/2023

Letter

Tolvaptan in portal hypertension: real life experience

DOI: 10.17235/reed.2022.9145/2022

Letter

Hemoperitoneum due to rupture of intra-abdominal varices

DOI: 10.17235/reed.2022.8937/2022

Digestive Diseases Image

Traumatic high flow arterioportal fistula. Correction by a covered stent

DOI: 10.17235/reed.2022.8724/2022

Letter

Stomal varices: an unusual cause of bleeding in liver cirrhosis

DOI: 10.17235/reed.2020.6470/2019

Letter to the Editor

Idiopathic portal hypertension with regard to thiopurine treatment

DOI: 10.17235/reed.2018.5256/2017

Letter to the Editor

POEMS syndrome and idiopathic portal hypertension: a possible association

DOI: 10.17235/reed.2017.4623/2016

Citation tools
Puente Á, Cabezas J, López Arias M, Fortea J, Arias M, Estébanez Á, et all. Influence of sustained viral response on the regression of fibrosis and portal hypertension in cirrhotic HCV patients treated with antiviral triple therapy. 4235/2016


Download to a citation manager

Download the citation for this article by clicking on one of the following citation managers:

Metrics
This article has received 275 visits.
This article has been downloaded 103 times.

Statistics from Dimensions


Statistics from Plum Analytics

Publication history

Received: 28/01/2016

Accepted: 13/09/2016

Online First: 19/12/2016

Published: 03/01/2017

Article revision time: 223 days

Article Online First time: 326 days

Article editing time: 341 days


Share
This article hasn't been rated yet.
Reader rating:
Valora este artículo:




Asociación Española de Ecografía Digestiva Sociedad Española de Endoscopia Digestiva Sociedad Española de Patología Digestiva
The Spanish Journal of Gastroenterology is the official organ of the Sociedad Española de Patología Digestiva, the Sociedad Española de Endoscopia Digestiva and the Asociación Española de Ecografía Digestiva
Cookie policy Privacy Policy Legal Notice © Copyright 2023 y Creative Commons. The Spanish Journal of Gastroenterology